In this exploratory/developmental application, we propose a novel approach to the investigation of the pathophysiology of autism, which is increasingly understood as a dysconnection syndrome. This proposal aims to provide further insights into the significance of cortico-cortical under-connectivity in autism, by relating ecologically meaningful measures of social impairment (a key dysfunction in autism) to the integrity of a network centered in perigenual anterior cingulate cortex, commonly implicated in social cognition. In addition, it aims to explore the relationship of ecologically meaningful measures of executive function (often impaired in autism) to a network based in dorsal anterior cingulate cortex, typically implicated in executive control. Unlike prior investigations of autism-related abnormalities in each of these networks, we propose to accomplish these aims using recently developed resting state blood-oxygenation level dependent fMRI measures of functional connectivity (i.e., inter-regional temporal coherence). We also propose to assess white matter integrity using diffusion tensor imaging and examine the relation between measures of structural integrity and functional connectivity. We hypothesize that autism-related compromises in neuronal connectivity will be related to indices of social and cognitive impairment, the Social Responsiveness Scale, and the Behavioral Response Inventory of Executive Functions, respectively. We propose to compare complete data from 30 adult males with high-functioning autism to 30 neurotypical controls group- matched for age, sex, handedness, full scale IQ, and socioeconomic status. This approach has the potential to inform our understanding of fundamental impairments in autism and consequently to transform current diagnostic and therapeutic approaches. PUBLIC HEALTH RELEVANCE: We propose to apply a novel approach to better understand the brain mechanisms involved in autism, a common condition that is associated with significant functional impairments, and immense suffering. We will study two brain networks that in neurotypical controls are commonly associated with social and cognitive control skills, both of which are thought to be disrupted in individuals with autism. We will enroll a group of adults with autism to compare their data to those of neurotypical volunteers. The proposed work introduces new techniques for the study of brain circuits in autism, and has the potential to further inform our understanding of the neural basis of autism, so that we can improve methods of diagnosis and treatment.